Brief overview of stability testing and its protocol to be followed for stability testing for herbal medicinal products.

1. Presented by:
Sudhindra Kini
Department of Pharmacognosy
Government college of pharmacy
Bangalore
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Submitted To:
Dr. Roopashree T. S
HOD- Department of Pharmacognosy
Government college of pharmacy
Bangalore

2.  Definition
 Objective
 Types of stability Studies
 Challenges in testing HMPs and steps to
overcome it
 Types of stability Testing
 Stability testing Protocol
 Reference
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3.  It’s the ability of formulation to retain its physical,
chemical, microbiological and toxicological parameter
same as that time of manufacture .
 Drug product remains within specifications established to
ensure its identity, strength, quality and purity.
 Stability – Chemical and Physical integrity of herbal
medicinal products.
 Over a given time period and under the influence of
environmental factors including temperature, humidity
and light.
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4.  To provide evidence on how the quality of active substance
varies with time and environmental factors
 To establish re- test period for active substance
 To establish shelf life of finished products.
 To recommend storage conditions.
 To evaluate the efficacy of drug.
 To develop suitable packing information for drug product
 To submit stability information for regulatory agencies.
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5. Types of stability study
1. Physical stability study:-
The original physical properties namely appearance, uniformity,
palatability, dissolution, and suspend ability are maintained.
2. Chemical stability study:-
Each and every active ingredient retains its chemical integrity as
well as potency specified on label, within the specified limits.
It involves drug assay and determination of drug degradation.
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6. Material used for stability studies:-
1. Active Pharmaceutical ingredient (API)
2. Finished pharmaceutical products
Stages in stability testing:-
1. Preformulation
2. Final product
3. Post marketing
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7. 3. Microbiological stability study:-
Sterility or resistance to microbial growth is maintained as per
the specified requirements.
4. Therapeutic stability study:-
The therapeutic effect remains unaltered.
5. Toxicological stability study:-
No valid increase in toxicity should occurs.
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8. Challenges in Stability testing of Herbal medicinal
products(HMP):-
 HMPs are complex in nature due to their high number of
constituents.
 Constituents belong to different chemical classes with
different analytical behaviour.
 Constituents sometimes have very low concentrations in the
finished product.
 Different requirements for the different types of extracts.
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9. Steps to overcome challenges:-
1. Use of markers for the HMPs.
 Marker concentration should be within ±5%
 When marker concentration is less in finished product
then variation of ±10%
2. Use of fingerprint chromatograms.
3. Use of GCMS, HPTLC, HPLC and spectroscopic technique.
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10. Introduction:-
 Working Party on Herbal Medicinal Products (WPHMP) of
the European Agency for the Evaluation of Medicinal
products (EMEA) suggests guidelines on herbal stability
testing.
Climatic Zones for Stability Testing:-
For stability testing purpose, the whole world has been
divided into four zones depending upon the environmental
conditions
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11.  The hygroscopic nature of extracts powder lead to flow-ability
and compressibility problems.
 Higher moisture content can lead greater risk of cohesion and
adhesion.
 The presence of variety of photochemical like alkaloids,
glycoside, phenolic, terpenoids and steroids makes botanical
chemically complex and pose challenge for analytical method
development.
 Presence of enzyme like glycosidase , esterases or oxidases play
important role in breakdown of plant secondary metabolites.
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12. 1. Stress testing substance
2. Accelerated stability testing
3. Long term stability testing products
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13.  Helps to identify the degradation products.
 Further help establish the degradation pathways and
the intrinsic stability of the molecule and validate the
stability indicating power of the analytical procedures
used.
 Nature of Stress testing depends on the individual drug
substance and the type of drug product involved.
 Generally conducted on a single batch of the drug
substance
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14.  The condition include the effect
 Temperatures (in 10°C increments (e.g., 50°C, 60°C,
etc.) above that for accelerated testing)
 Humidity (e.g., 75% RH or greater) where
appropriate, oxidation, and photolysis on the drug
substance.
 The testing should also evaluate the susceptibility of
the drug substance to hydrolysis across a wide range
of pH values when in solution or suspension.
 Perform phytochemical analysis for constitutes in
given sample of HMPs by HPLC, HPTLC.
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15.  The substance or medicinal product is challenged by
a controlled exaggerated stress (storage conditions)
over a short time, so that the rate of degradation
reaction is enhanced.
 In short period time, stability data can be obtained
(3 – 6 months)
 Samples are stored at 400C ± 20C; 75 % ± 5 % RH for a
period of 6 months
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16. Procedure:-
1. Note down Description, identification, ph, viscosity,
assay, heavy metals & microbial purity.
2. Above parameter should match those specified in
monographs or label.
3. Transfer HMPs
a). PET Bottle with Al- cap, containing Rubber cork
b). Glass Bottle with Al- cap, containing Rubber cork.
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17. 4. 1st set
- 25°C ± 2°C / 60% RH ± 5% --------> Control condition
5. 2nd set
- 40°C ± 2°C / 75% RH ± 5% -------> Accelerated
condition
6. Carry out sampling at various intervals( 0 ,1,
3, 4 ,5,……… months)
7.Perform phytochemical analysis for constitutes in given
sample of HMPs by HPLC, HPTLC.
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18.  Evaluation of the physical, chemical and
microbiological characteristics of a drug product over
the expected duration of shelf-life under
recommended storage conditions and in the proposed
container/closure system.
Storage of stability samples:-
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STUDY Temperature Relative
Humidity
Time period
General 25°C ± 2°C 60% RH ± 5% 12 months
General 30°C ± 2°C 65% RH ± 5% 12 months
Refrigerator 5°C ± 3°C ------ 12 months
Freezer -20°C ± 3°C ------ 12 months

19. Stability samples testing frequency:-
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Category Selection of Batches Frequency of Testing
New Drug Product 1st 3 Batch 3,6,9,12,18,24,36
months
& 1 year after expiry
Subsequent Batches 1 Batch every year 6,9,12,18,24,36
months
& 1 year after expiry
Product with primary
change in packing
3 Batch 3, 6,9,12,18,24,36
months
& 1 year after expiry
Product with
secondary change in
packing
3 Batch 3, 6,9,12,18,24,36
months
& 1 year after expiry

20. Protocol is a document describing the basic components
of a well-controlled stability study.
A well-planned stability protocol should contain the
following information:-
1. Selection of batches and samples - In general, this
selection should constitute a random sample from pilot or
production batches that may involve a single batch or 2-3
batches
2. Test attributes - The tests that monitor the quality,
potency, purity, and identity that are expected to vary upon
storage are chosen as stability tests
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21. 3. Analytical procedures - Procedures given in the official
compendia should be followed and if alternate methods are to
be used, they need to be duly validated
4. Acceptance criteria - This should be fixed beforehand in
the form of statistical limits for the results manifested in
computable terms and pass or fail for qualitative tests
5. Storage conditions - These are based upon the marketing
climatic zone of the drug.
Storage condition such that thermal stability as well sensitivity
to moisture can be tested.
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STUDY Temperature Relative
Humidity
Time period
General 25°C ± 2°C 60% RH ± 5% 12 months
General 30°C ± 2°C 65% RH ± 5% 12 months
Refrigerator 5°C ± 3°C ------ 12 months
Freezer
Long Term -20°C ± 3°C ------ 12 months

22. 6. Storage period –
It generally extend from minimum of 3 or 6 months in
accelerated and stress testing and up to 12, 18, or 60 months
in ongoing or follow-up stability testing.
7. Testing frequency –
It should be sufficient to establish the stability profile of the
drug Test schedules for different types of stability testing.
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23. 8. Sampling plan - It involves devising for the number of
samples to be placed in the stability chambers and taking out
of the charged batch so as to cover the entire study.
9. Container closure system - The testing in actual
containers as well as closures scheduled for marketing, are to
be tested separately with proper orientation of storage of
containers.
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24. 10. Evaluation - The data on quantitative attribute is
analysed to determine the time duration at which 95%
one-sided confidence limit for the mean curve
intersects the acceptance criterion.
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25. 11. Statements, labelling - A storage statement, retest
period, and re-test date based on the stability
evaluation of the drug substance should be established
for the labelling.
Labelling specification should match as those
mentioned by regulatory authority.
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26.  Roth-Ehrang, Asche, Hubbert, Kruse, Lutz-Röder, Poetsch ,
Tegtmeier , Wiedemann and Steinhoff : Stability Testing of
Herbal Medicinal Products.
 Guideline on quality of herbal medicinal products /
traditional herbal medicinal products(CPMP/QWP/2819/00,
Rev 1)
 Guideline on Quality of Combination Herbal Medicinal
Products / Traditional Herbal Medicinal Products (Doc. Ref.
EMEA/HMPC/CVMP/214869/2006)
 Guideline on specifications: test procedures and acceptance
criteria for herbal substances, herbal preparations and
herbal medicinal products/traditional herbal medicinal
products’ (CPMP/QWP/2820/00, EMEA/CVMP/815/00)
 ICH Guidelines Stability Testing of new Drug Substances and
Products (CPMP/ICH/2736/990)
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